The purpose of this project is to study the role of the immune system in connective tissue metabolism. We have shown that the production of collagenase by activated macrophages is regulated by prostaglandins which are produced by these cells. An increase in the synthesis of prostaglandins is required prior to the production of collagenase by macrophages whether they are activated by endotoxin or lymphokines. The prostaglandins produced by activated macrophages appear to regulate collagenase production by modulating cAMP levels within these cells. Other studies dealing with the role of the immune system in bone resorption have revealed a lymphocyte proliferative defect in osteopetrotic mice. In another osteopetrotic animal model, the toothless rat, the affected animals have macrophages which are defective in their production of prostaglandins.